Science, serendipity, coincidence, and the Oregonator at the University of Oregon, 1969-1974.

This historical review of the development of the Oregonator model of the Belousov-Zhabotinsky reaction is based on a lecture Dick Field presented during IrvFest2015-Celebrating a founding father of chaos!, a meeting in commemoration of Irving R. Epstein's 70 th birthday. For Dick's 80 th birthday festschrift, we focus here on the five papers in the series named "Oscillations in chemical systems," published in 1972 [Noyes et al., J. Am. Chem. Soc. 94, 1394-1395 (1972); Field et al., J. Am. Chem. Soc. 94, 8649-8664 (1972); Field and Noyes, Nature 237, 390-392 (1972)] and 1974 [Field and Noyes, J. Chem. Phys. 60, 1877-1884 (1974); Field and Noyes, J. Am. Chem. Soc. 96, 2001-2006 (1974)].

Geographic tongue as a reaction-diffusion system.

Geographic tongue or benign migratory glossitis is a condition of an unknown cause characterized by chronic lesions that slowly migrate across the surface of the tongue. The condition's characteristic wavefronts suggest that it can be modeled as a reaction-diffusion system. Here, we present a model for geographic tongue pattern evolution using reaction-diffusion equations applied to portions of spheroids and paraboloids that approximate a tongue shape. We demonstrate that the observed patterns of geographic tongue lesions can be explained by propagating reaction-diffusion waves on these variably curved surfaces.

Genetic and neurophysiological correlates of the age of onset of alcohol use disorders in adolescents and young adults.

Discrete time survival analysis was used to assess the age-specific association of event-related oscillations (EROs) and CHRM2 gene variants on the onset of regular alcohol use and alcohol dependence. The subjects were 2,938 adolescents and young adults ages 12-25. Results showed that the CHRM2 gene variants and ERO risk factors had hazards which varied considerably with age. The bulk of the significant age-specific associations occurred in those whose age of onset was under 16. These associations were concentrated in those subjects who at some time took an illicit drug. These results are consistent with studies which associate greater rates of alcohol dependence among those who begin drinking at an early age. The age specificity of the genetic and neurophysiological factors is consistent with recent studies of adolescent brain development, which locate an interval of heightened vulnerability to substance use disorders in the early to mid teens.

Genetic influences vary by age and sex: Trajectories of the association of cholinergic system variants and theta band event related oscillations.

To characterize systemic changes in genetic effects on brain development, the age variation of the associations of cholinergic genetic variants and theta band event-related oscillations (EROs) was studied in a sample of 2140 adolescents and young adults, ages 12 to 25 from the COGA prospective study. The theta band EROs were elicited in visual and auditory oddball (target detection) tasks and measured by EEG recording. Associations were found to vary with age, sex, task modality (auditory or visual), and scalp locality. Seven of the twenty-one muscarinic and nicotinic cholinergic SNPs studied in the analysis, from CHRM2, CHRNA3, CHRNA5, and CHRNB4, had significant effects on theta band EROs with considerable age spans for some sex-modality combination. No SNP-age-modality combination had significant effects in the same direction for males and females. Results suggest that nicotinic receptor associations are stronger before age 18, while muscarinic receptor associations are stronger after age 18.

Topography, power, and current source density of θ oscillations during reward processing as markers for alcohol dependence.

Recent studies have linked alcoholism with a dysfunctional neural reward system. Although several electrophysiological studies have explored reward processing in healthy individuals, such studies in alcohol-dependent individuals are quite rare. The present study examines theta oscillations during reward processing in abstinent alcoholics. The electroencephalogram (EEG) was recorded in 38 abstinent alcoholics and 38 healthy controls as they performed a single outcome gambling task, which involved outcomes of either loss or gain of an amount (10 or 50¢) that was bet. Event-related theta band (3.0-7.0 Hz) power following each outcome stimulus was computed using the S-transform method. Theta power at the time window of the outcome-related negativity (ORN) and positivity (ORP) (200-500 ms) was compared across groups and outcome conditions. Additionally, behavioral data of impulsivity and task performance were analyzed. The alcoholic group showed significantly decreased theta power during reward processing compared to controls. Current source density (CSD) maps of alcoholics revealed weaker and diffuse source activity for all conditions and weaker bilateral prefrontal sources during the Loss 50 condition when compared with controls who manifested stronger and focused midline sources. Furthermore, alcoholics exhibited increased impulsivity and risk-taking on the behavioral measures. A strong association between reduced anterior theta power and impulsive task-performance was observed. It is suggested that decreased power and weaker and diffuse CSD in alcoholics may be due to dysfunctional neural reward circuitry. The relationship among alcoholism, theta oscillations, reward processing, and impulsivity could offer clues to understand brain circuitries that mediate reward processing and inhibitory control.

Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence.

Event-related brain oscillations (EROs) represent highly heritable neuroelectrical correlates of human perception and cognitive performance that exhibit marked deficits in patients with various psychiatric disorders. We report the results of the first genome-wide association study (GWAS) of an ERO endophenotype-frontal theta ERO evoked by visual oddball targets during P300 response in 1,064 unrelated individuals drawn from a study of alcohol dependence. Forty-two SNPs of the Illumina HumanHap 1 M microarray were selected from the theta ERO GWAS for replication in family-based samples (N = 1,095), with four markers revealing nominally significant association. The most significant marker from the two-stage study is rs4907240 located within ARID protein 5A gene (ARID5A) on chromosome 2q11 (unadjusted, Fisher's combined P = 3.68 × 10⁻6). However, the most intriguing association to emerge is with rs7916403 in serotonin receptor gene HTR7 on chromosome 10q23 (combined P = 1.53 × 10⁻4), implicating the serotonergic system in the neurophysiological underpinnings of theta EROs. Moreover, promising SNPs were tested for association with diagnoses of alcohol dependence (DSM-IV), revealing a significant relationship with the HTR7 polymorphism among GWAS case-controls (P = 0.008). Significant recessive genetic effects were also detected for alcohol dependence in both case-control and family-based samples (P = 0.031 and 0.042, respectively), with the HTR7 risk allele corresponding to theta ERO reductions among homozygotes. These results suggest a role of the serotonergic system in the biological basis of alcohol dependence and underscore the utility of analyzing brain oscillations as a powerful approach to understanding complex genetic psychiatric disorders.

Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence.

BACKGROUND: Endophenotypes reflect more proximal effects of genes than diagnostic categories, hence providing a more powerful strategy in searching for genes involved in complex psychiatric disorders. There is strong evidence suggesting the P3 amplitude of the event-related potential (ERP) as an endophenotype for the risk of alcoholism and other disinhibitory disorders. Recent studies demonstrated a crucial role of corticotropin releasing hormone receptor 1 (CRHR1) in the environmental stress response and ethanol self-administration in animal models. The aim of the present study was to test the potential associations between single-nucleotide polymorphisms (SNPs) in the CRHR1 gene and the quantitative trait, P3 amplitude during the processing of visual target signals in an oddball paradigm, as well as alcohol dependence diagnosis. METHODS: We analyzed a sample from the Collaborative Study on the Genetics of Alcoholism (COGA) comprising 1049 Caucasian subjects from 209 families (including 472 alcohol-dependent individuals). Quantitative transmission disequilibrium test (QTDT) and family-based association test (FBAT) were used to test the association, and false discovery rate (FDR) was applied to correct for multiple comparisons. RESULTS: Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. CONCLUSIONS: Our results suggest that CRHR1 may be involved in modulating the P3 component of the ERP during information processing and in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders.

Theta oscillations during the processing of monetary loss and gain: a perspective on gender and impulsivity.

Event-related oscillations (EROs) have proved to be very useful in the understanding of a variety of neurocognitive processes including reward/outcome processing. In the present study, theta power (4.0-7.0 Hz) following outcome stimuli in the time window of the N2-P3 complex (200-500 ms) was analyzed in healthy normals (20 males and 20 females) while performing a gambling task that involved monetary loss and gain. The main aim was to analyze outcome processing in terms of event-related theta power in the context of valence, amount, gender, and impulsivity. The S-transform was used for the signal processing of the ERO data in terms of time-frequency-power. Results from filtered waveforms showed a partially consistent phase-alignment of the increased theta activity corresponding to N2 and P3 components following the outcome stimuli. Gain conditions produced more theta power than loss conditions. While there was anterior involvement in both gain and loss, posterior activation was stronger during gain conditions than during loss conditions. Females exhibited posterior maxima during gain conditions while males had an anterior maxima during both loss and gain conditions. The current source density of theta activity in females involved larger areas with a bilateral frontal activity while males predominantly had a frontal midline activity. Theta power was significantly higher in females than males across all conditions. Low theta (4.0-5.5 Hz) predominantly contributed to the posterior activity during gain conditions. High theta (5.5-7.0 Hz) was more associated with impulsivity measures than low theta activity. These findings may offer valuable clues to understand outcome processing, impulsivity, and gender differences.

Genetic correlates of the development of theta event related oscillations in adolescents and young adults.

The developmental trajectories of theta band (4-7Hz) event-related oscillations (EROs), a key neurophysiological constituent of the P3 response, were assessed in 2170 adolescents and young adults ages 12 to 25. The theta EROs occurring in the P3 response, important indicators of neurocognitive function, were elicited during the evaluation of task-relevant target stimuli in visual and auditory oddball tasks. Associations between the theta EROs and genotypic variants of 4 KCNJ6 single nucleotide polymorphisms (SNPs) were found to vary with age, sex, scalp location, and task modality. Three of the four KCNJ6 SNPs studied here were found to be significantly associated with the same theta EROs in adults in a previous family genome wide association study. Since measures of the P3 response have been found to be a useful endophenotypes for the study of a number of clinical and behavioral disorders, studies of genetic effects on its development in adolescents and young adults may illuminate neurophysiological factors contributing to the onset of these conditions.

A KCNJ6 gene polymorphism modulates theta oscillations during reward processing.

Event related oscillations (EROs) are heritable measures of neurocognitive function that have served as useful phenotype in genetic research. A recent family genome-wide association study (GWAS) by the Collaborative Study on the Genetics of Alcoholism (COGA) found that theta EROs during visual target detection were associated at genome-wide levels with several single nucleotide polymorphisms (SNPs), including a synonymous SNP, rs702859, in the KCNJ6 gene that encodes GIRK2, a G-protein inward rectifying potassium channel that regulates excitability of neuronal networks. The present study examined the effect of the KCNJ6 SNP (rs702859), previously associated with theta ERO to targets in a visual oddball task, on theta EROs during reward processing in a monetary gambling task. The participants were 1601 adolescent and young adult offspring within the age-range of 17-25years (800 males and 801 females) from high-dense alcoholism families as well as control families of the COGA prospective study. Theta ERO power (3.5-7.5Hz, 200-500ms post-stimulus) was compared across genotype groups. ERO theta power at central and parietal regions increased as a function of the minor allele (A) dose in the genotype (AA>AG>GG) in both loss and gain conditions. These findings indicate that variations in the KCNJ6 SNP influence magnitude of theta oscillations at posterior loci during the evaluation of loss and gain, reflecting a genetic influence on neuronal circuits involved in reward-processing. Increased theta power as a function of minor allele dose suggests more efficient cognitive processing in those carrying the minor allele of the KCNJ6 SNPs. Future studies are needed to determine the implications of these genetic effects on posterior theta EROs as possible "protective" factors, or as indices of delays in brain maturation (i.e., lack of frontalization).

A genome wide association study of fast beta EEG in families of European ancestry.

BACKGROUND: Differences in fast beta (20-28Hz) electroencephalogram (EEG) oscillatory activity distinguish some individuals with psychiatric and substance use disorders, suggesting that it may be a useful endophenotype for studying the genetics of disorders characterized by neural hyper-excitability. Despite the high heritability estimates provided by twin and family studies, there have been relatively few genetic studies of beta EEG, and to date only one genetic association finding has replicated (i.e., GABRA2). METHOD: In a sample of 1564 individuals from 117 families of European Ancestry (EA) drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Genome-Wide Association Study (GWAS) on resting-state fronto-central fast beta EEG power, adjusting regression models for family relatedness, age, sex, and ancestry. To further characterize genetic findings, we examined the functional and behavioral significance of GWAS findings. RESULTS: Three intronic variants located within DSE (dermatan sulfate epimerase) on 6q22 were associated with fast beta EEG at a genome wide significant level (p<5×10-8). The most significant SNP was rs2252790 (p<2.6×10-8; MAF=0.36; ß=0.135). rs2252790 is an eQTL for ROS1 expressed most robustly in the temporal cortex (p=1.2×10-6) and for DSE/TSPYL4 expressed most robustly in the hippocampus (p=7.3×10-4; ß=0.29). Previous studies have indicated that DSE is involved in a network of genes integral to membrane organization; gene-based tests indicated that several variants within this network (i.e., DSE, ZEB2, RND3, MCTP1, and CTBP2) were also associated with beta EEG (empirical p<0.05), and of these genes, ZEB2 and CTBP2 were associated with DSM-V Alcohol Use Disorder (AUD; empirical p<0.05).' DISCUSSION: In this sample of EA families enriched for AUDs, fast beta EEG is associated with variants within DSE on 6q22; the most significant SNP influences the mRNA expression of DSE and ROS1 in hippocampus and temporal cortex, brain regions important for beta EEG activity. Gene-based tests suggest evidence of association with related genes, ZEB2, RND3, MCTP1, CTBP2, and beta EEG. Converging data from GWAS, gene expression, and gene-networks presented in this study provide support for the role of genetic variants within DSE and related genes in neural hyperexcitability, and has highlighted two potential candidate genes for AUD and/or related neurological conditions: ZEB2 and CTBP2. However, results must be replicated in large, independent samples.

Propagation failure dynamics of wave trains in excitable systems.

We report experimental and numerical results on temporal patterns of propagation failures in reaction-diffusion systems. Experiments employ the 1,4-cyclohexanedione Belousov-Zhabotinsky reaction. The propagation failures occur in the frontier region of the wave train and can profoundly affect its expansion speed. The specific rhythms observed vary from simple periodic to highly complex and possibly chaotic sequences. All but the period-1 sequences are found in the transition region between "merging" and "tracking" dynamics, which correspond to wave behavior caused by two qualitatively different types of anomalous dispersion relations.

Delta, theta, and alpha event-related oscillations in alcoholics during Go/NoGo task: Neurocognitive deficits in execution, inhibition, and attention processing.

Higher impulsivity observed in alcoholics is thought to be due to neurocognitive functional deficits involving impaired inhibition in several brain regions and/or neuronal circuits. Event-related oscillations (EROs) offer time-frequency measure of brain rhythms during perceptual and cognitive processing, which provide a detailed view of neuroelectric oscillatory responses to external/internal events. The present study examines evoked power (temporally locked to events) of oscillatory brain signals in alcoholics during an equal probability Go/NoGo task, assessing their functional relevance in execution and inhibition of a motor response. The current study hypothesized that increases in the power of slow frequency bands and their topographical distribution is associated with tasks that have increased cognitive demands, such as the execution and inhibition of a motor response. Therefore, it is hypothesized that alcoholics would show lower spectral power in their topographical densities compared to controls. The sample consisted of 20 right-handed abstinent alcoholic males and 20 age and gender-matched healthy controls. Evoked delta (1.0-3.5Hz; 200-600ms), theta (4.0-7.5Hz; 200-400ms), slow alpha (8.0-9.5Hz; 200-300ms), and fast alpha (10.0-12.5Hz; 100-200ms) ERO power were compared across group and task conditions. Compared to controls, alcoholics had higher impulsiveness scores on the Barrett Impulsiveness Scale (BIS-11) and made more errors on Go trials. Alcoholics showed significantly lower evoked delta, theta, and slow alpha power compared to controls for both Go and NoGo task conditions, and lower evoked fast alpha power compared to controls for only the NoGo condition. The results confirm previous findings and are suggestive of neurocognitive deficits while executing and suppressing a motor response. Based on findings in the alpha frequency ranges, it is further suggested that the inhibitory processing impairments in alcoholics may arise from inadequate early attentional processing with respect to the stimulus related aspects/semantic memory processes, which may be reflected in lower posterio-temporal evoked fast alpha power. It can thus be concluded that alcoholics show neurocognitive deficits in both execution and suppression of a motor response and inadequate early attentional processing with respect to the semantic memory/stimulus related aspects while suppressing a motor response.

Gender modulates the development of theta event related oscillations in adolescents and young adults.

The developmental trajectories of theta band (4-7 Hz) event-related oscillations (EROs), a key neurophysiological constituent of the P3 response, were assessed in 2170 adolescents and young adults ages 12 to 25. The theta EROs occurring in the P3 response, important indicators of neurocognitive function, were elicited during the evaluation of task-relevant target stimuli in visual and auditory oddball tasks. These tasks call upon attentional and working memory resources. Large differences in developmental rates between males and females were found; scalp location and task modality (visual or auditory) differences within males and females were small compared to gender differences. Trajectories of interregional and intermodal correlations between ERO power values exhibited increases with age in both genders, but showed a divergence in development between auditory and visual systems during ages 16 to 21. These results are consistent with previous electrophysiological and imaging studies and provide additional temporal detail about the development of neurophysiological indices of cognitive activity. Since measures of the P3 response has been found to be a useful endophenotypes for the study of a number of clinical and behavioral disorders, studies of its development in adolescents and young adults may illuminate neurophysiological factors contributing to the onset of these conditions.

Deficient Event-Related Theta Oscillations in Individuals at Risk for Alcoholism: A Study of Reward Processing and Impulsivity Features.

BACKGROUND: Individuals at high risk to develop alcoholism often manifest neurocognitive deficits as well as increased impulsivity. Event-related oscillations (EROs) have been used to effectively measure brain (dys)function during cognitive tasks in individuals with alcoholism and related disorders and in those at risk to develop these disorders. The current study examines ERO theta power during reward processing as well as impulsivity in adolescent and young adult subjects at high risk for alcoholism. METHODS: EROs were recorded during a monetary gambling task (MGT) in 12-25 years old participants (N = 1821; males = 48%) from high risk alcoholic families (HR, N = 1534) and comparison low risk community families (LR, N = 287) from the Collaborative Study on the Genetics of Alcoholism (COGA). Impulsivity scores and prevalence of externalizing diagnoses were also compared between LR and HR groups. RESULTS: HR offspring showed lower theta power and decreased current source density (CSD) activity than LR offspring during loss and gain conditions. Younger males had higher theta power than younger females in both groups, while the older HR females showed more theta power than older HR males. Younger subjects showed higher theta power than older subjects in each comparison. Differences in topography (i.e., frontalization) between groups were also observed. Further, HR subjects across gender had higher impulsivity scores and increased prevalence of externalizing disorders compared to LR subjects. CONCLUSIONS: As theta power during reward processing is found to be lower not only in alcoholics, but also in HR subjects, it is proposed that reduced reward-related theta power, in addition to impulsivity and externalizing features, may be related in a predisposition to develop alcoholism and related disorders.

Reward processing deficits and impulsivity in high-risk offspring of alcoholics: A study of event-related potentials during a monetary gambling task.

BACKGROUND: Individuals at high risk to develop alcoholism often manifest neurocognitive deficits as well as increased impulsivity. The goal of the present study is to elucidate reward processing deficits, externalizing disorders, and impulsivity as elicited by electrophysiological, clinical and behavioral measures in subjects at high risk for alcoholism from families densely affected by alcoholism in the context of brain maturation across age groups and gender. METHODS: Event-related potentials (ERPs) and current source density (CSD) during a monetary gambling task (MGT) were measured in 12-25 year old offspring (N=1864) of families in the Collaborative Study on the Genetics of Alcoholism (COGA) Prospective study; the high risk (HR, N=1569) subjects were from families densely affected with alcoholism and the low risk (LR, N=295) subjects were from community families. Externalizing disorders and impulsivity scores were also compared between LR and HR groups. RESULTS: HR offspring from older (16-25 years) male and younger (12-15 years) female subgroups showed lower P3 amplitude than LR subjects. The amplitude decrement was most prominent in HR males during the loss condition. Overall, P3 amplitude increase at anterior sites and decrease at posterior areas were seen in older compared to younger subjects, suggesting frontalization during brain maturation. The HR subgroups also exhibited hypofrontality manifested as weaker CSD activity during both loss and gain conditions at frontal regions. Further, the HR subjects had higher impulsivity scores and increased prevalence of externalizing disorders. P3 amplitudes during the gain condition were negatively correlated with impulsivity scores. CONCLUSIONS: Older male and younger female HR offspring, compared to their LR counterparts, manifested reward processing deficits as indexed by lower P3 amplitude and weaker CSD activity, along with higher prevalence of externalizing disorders and higher impulsivity scores. SIGNIFICANCE: Reward related P3 is a valuable measure reflecting neurocognitive dysfunction in subjects at risk for alcoholism, as well as to characterize reward processing and brain maturation across gender and age group.

Dynamics of excitation pulses with attractive interaction: kinematic analysis and chemical wave experiments.

We present a theoretical analysis of stacking and destacking wave trains in excitable reaction-diffusion systems with anomalous velocity-wavelength dependence. For linearized dispersion relations, kinematic analysis yields an analytical function that rigorously describes front trajectories. The corresponding accelerations have exactly one extremum that slowly decays with increasing pulse number. For subsequent pulses these maxima occur with a lag time equal to the inverse slope of the linearized dispersion curve. These findings are reproduced in experiments with chemical waves in the 1,4-cyclohexanedione Belousov-Zhabotinsky reaction but should be also applicable to step bunching on crystal surfaces and certain traffic phenomena.

Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking.

Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28

Nonreplication of an association of SGIP1 SNPs with alcohol dependence and resting theta EEG power.

A recent study in a sample of Plains Indians showed association between eight single nucleotide polymorphisms (SNPs) located in the SGIP1 gene and resting θ electroencephalogram (EEG) power. This association appeared to generalize to alcohol use disorders, for which EEG power is a potential endophenotype. We analyzed a large, diverse sample for replication of the association of these implicated SGIP1 SNPs (genotyped on the Illumina 1M platform) with alcohol dependence (N=3988) and θ EEG power (N=1066). We found no evidence of association of the earlier implicated SGIP1 SNPs with either alcohol dependence or θ EEG power (all P>0.15) in this sample. The earlier implicated SNPs located in SGIP1 gene showed no association with alcohol dependence or θ EEG power in this sample of individuals with European and/or African ancestry. This failure to replicate may be the result of differences in ancestry between this sample and the original sample.

Dysfunctional reward processing in male alcoholics: an ERP study during a gambling task.

OBJECTIVE: A dysfunctional neural reward system has been shown to be associated with alcoholism. The current study aims to examine reward processing in male alcoholics by using event-related potentials (ERPs) as well as behavioral measures of impulsivity and risk-taking. METHODS: Outcome-related negativity (ORN/N2) and positivity (ORP/P3) derived from a single outcome gambling task were analyzed using a mixed model procedure. Current density was compared across groups and outcomes using standardized low resolution electromagnetic tomography (sLORETA). Behavioral scores were also compared across groups. Correlations of ERP factors with behavioral and impulsivity factors were also analyzed. RESULTS: Alcoholics showed significantly lower amplitude than controls during all outcome conditions for the ORP component and decreased amplitude during the loss conditions for the ORN component. Within conditions, gain produced higher amplitudes than loss conditions. Topographically, both groups had an anterior focus during loss conditions and posterior maxima during gain conditions, especially for the ORN component. Decreased ORP current density at cingulate gyrus and less negative ORN current density at sensory and motor areas characterized the alcoholics. Alcoholics had higher levels of impulsivity and risk-taking features than controls. CONCLUSIONS: Deficient outcome/reward processing and increased impulsivity and risk-taking observed in alcoholics may be at least partly due to reward deficiency and/or dysfunctional reward circuitry in the brain, suggesting that alcoholism can be considered as part of the cluster of the reward deficiency syndrome (RDS).